scholarly journals Animal model investigation suggests betamethasone alters the pharmacokinetics of amikacin

ADMET & DMPK ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 279-283
Author(s):  
Seth Kwabena Amponsah ◽  
Kwabena Frimpong-Manso Opuni ◽  
Ama Asiedua Donkor
Keyword(s):  
Animal Model ◽  
Fold Increase ◽  
Model Investigation ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Term Delivery ◽  
Preterm Newborns ◽  
Immature Immune System

Corticosteroids, such as betamethasone, are sometimes administered to women who are at risk of pre-term delivery. These corticosteroids cross the placenta to the fetus and decrease respiratory distress syndrome in preterm newborns. Preterm newborns are often susceptible to infections partly due to their immature immune system. Amikacin is one of the aminoglycosides used in the treatment of newborn infections. There is, however, a dearth of information on the effect of prenatal corticosteroids on the disposition of aminoglycosides administered to newborns days later. We evaluated the effect of pre-administration of betamethasone on the disposition of amikacin, 72 h after last dose of betamethasone, using an animal model. The pharmacokinetic parameters of rats administered betamethasone followed by amikacin vis-a-vis rats administered saline followed by amikacin were as follows: Cmax; 16.6 μmol L-1 vs. 31.4 μmol L-1, AUC0→8; 26.8 μmol h L-1 vs. 153.5 μmol h L-1, Ke; 0.26 h-1 vs. 0.18 h-1, and t1/2; 2.6 h vs. 3.9 h, respectively. About a 1.5-fold increase in the elimination of amikacin was observed in the Sprague-Dawley rats pre-treated with betamethasone compared with those pre-treated with saline. This ultimately led to differences in the other pharmacokinetic parameters amongst the two groups of rats. Although an animal model investigation showed some level of interaction, a follow-up study in preterm newborns where possible interaction of the two drugs is studied later than Day 1, is recommended.

Ultrastructural investigation of spontaneous pituitary gonadotroph cell adenomas in aging Sprague-Dawley rats

1983 ◽  
Vol 41 ◽  
pp. 702-703
Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs
Keyword(s):  
Electron Microscopy ◽  
Animal Model ◽  
Epoxy Resin ◽  
Immunoelectron Microscopy ◽  
Tumor Type ◽  
Gonadal Function ◽  
Sprague Dawley ◽  
Male And Female ◽  
Reticulin Fibers ◽  
Sprague Dawley Rats

Gonadotroph cell adenomas of the pituitary are infrequent in human patients and are not invariably associated with altered gonadal function. To date, no animal model of this tumor type exists. Herein, we describe spontaneous gonadotroph cell adenomas in old male and female Sprague-Dawley rats by histology, immunocytology and electron microscopy.The material consisted of the pituitaries of 27 male and 38 female Sprague Dawley rats, all 26 months of age or older, removed at routine autopsy. Sections of formal in-fixed, paraffin-embedded tissue were stained with hematoxylin-phloxine-saffron (HPS), the PAS method and the Gordon-Sweet technique for the demonstration of reticulin fibers. For immunostaining, sections were exposed to anti-rat β-LH, anti-ratβ-TSH, anti-rat PRL, anti-rat GH and anti-rat ACTH 1-39. For electron microscopy, tissue was fixed in 2.5% glutaraldehyde, postfixed in 1% OsO4 and embedded in epoxy-resin. Tissue fixed in 10% formalin, embedded in epoxy resin without osmification, was used for immunoelectron microscopy.

Pharmacokinetic Interaction between Asari Radix et Rhizoma and Dried Ginger (Zingiber officinalis) in Rats

2021 ◽  
Vol 17 ◽  
Author(s):  
Xingxing Zhuang ◽  
Li Zhou ◽  
Renhua Miao ◽  
Shoudong Ni ◽  
Meng Li
Keyword(s):  
High Performance ◽  
Pharmacokinetic Interaction ◽  
Raw Material ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Active Components ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass ◽  
Student’S T ◽  
Student’S T Test

Introduction:: Asari Radix et Rhizoma (ARR) and dried ginger (Zingiber officinalis) (DG) are often used together in drug preparations in traditional Chinese medicine (TCM) to treat respiratory diseases including cold, bronchitis and pneumonia. Previous studies suggested that ARR and/or DG may influence the pharmacokinetics of other herbal components. In the current study, we examined pharmacokinetic interactions between ARR and DG in rats after oral administration. Methods:: We developed a method based on ultra-high-performance liquid chromatography-tandem mass spectrometry to simultaneously measure serum concentrations of two active components each in ARR (L-asarinin and sesamin) and DG (6-gingerol and 6-shogaol). Adult Sprague-Dawley rats were starved overnight, then given ARR extract, DO extract, or a co-decoction of ARR and DG by gastric gavage (6 g raw material per kg body weight; n = 6 per group). Blood samples were collected prior to drug administration and at the following times (h) afterward: 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0 and 24.0. Pharmacokinetic parameters were compared using Student’s t test for independent samples. Results:: A simple, rapid, sensitive analytical method has been developed to detect four bioactive components simultaneously in the ARR-DG herbal pair. Pharmacokinetic parameters including Cmax, Tmax, T1/2 and AUC(0~t) were calculated using the non-compartmental model with the DAS 2.0 pharmacokinetic software. For L-asarinin, Tmax was 2.00 ± 0.00 h in ARR animals and 1.67±0.26 h in ARR-DG animals (P<0.05), T1/2 was 8.58 ± 1.75 h in ARR and 11.93 ± 2.13 h in ARR-DG (P<0.05). For 6-gingerol, Cmax was 350.48 ± 23.85 ng/mL in DG animals and 300.21 ± 20.02 ng/mL in ARR-DG (P<0.01), Tmax was 2.83 ± 0.41 h in DG and 2.17 ± 0.41 h in ARR-DG (P<0.05) and AUC(0~t) was 1.93 ± 0.15 mg/mL•h in ARR and 1.70 ± 0.15 mg/mL•h in ARR-DG (P<0.05). For 6-shogaol, Cmax was 390.28 ± 26.02 ng/mL in DG animals and 455.63 ± 31.01 ng/mL in ARR-DG (P<0.01), Tmax was 2.93 ± 0.10 h in DG and 1.92 ± 0.10 h in ARR-DG (P<0.01), T1/2 was 3.74 ± 0.29 h in DG and 3.28 ± 0.22 h in ARR-DG (P<0.01), and AUC(0~t) was 2.15 ± 0.18 mg/mL•h in DG and 2.73 ± 0.15 mg/mL•h in ARR-DG (P<0.01). Conclusions:: Pharmacokinetic interations between ARR and DG decrease Tmax, increase T1/2 but do not affect overall bioavailability of L-asarinin in ARR. The interactions in ARR-DG decrease Cmax and Tmax but increase T1/2 and AUC(0~t) of 6-gingerol in DG. The interactions increase Cmax and AUC(0~t) but decrease Tmax and T1/2 of 6- shogaol in DG. Interactions in ARR-DG do not affect the pharmacokinetics of sesamin.

Recombinant human regenerating gene 4 attenuates the severity of osteoarthritis by promoting the proliferation of articular chondrocyte in an animal model

2021 ◽  
Vol 14 ◽  
Author(s):  
Xue-jia Li ◽  
Fei Zhu ◽  
Bo Li ◽  
Dong Zhang ◽  
Cheng-Wei Liang
Keyword(s):  
Risk Factors ◽  
Animal Model ◽  
Sprague Dawley ◽  
Articular Chondrocyte ◽  
Chondrocyte Proliferation ◽  
Histological Changes ◽  
Proper Role ◽  
Sprague Dawley Rats ◽  
Gene 4

Introduction: Osteoarthritis (OA) is a dominant cause of morbidity and disability. As a chronic disease, its etiological risk factors and most therapies at present, are empirical and symptomatic. Regenerating gene 4 (Reg4) is involved in cell growth, survival, regeneration, adhesion, and resistance to apoptosis, which are partially thought to be the pathogenic mechanisms of OA. However, the proper role of Reg4 in OA is still unknown. Methods: In this study, a consecutive administration of rhReg4 was applied to normal Sprague-Dawley rats or rats after OA induction. Histological changes and chondrocyte proliferation in the articular cartilage were measured. Results: We found that RhReg4 promotes chondrocyte proliferation in normal rats, and RhReg4 attenuated the severity of OA in rats by promoting chondrocytes’ proliferation in OA rats. Conclusion: In conclusion, recombinant human regenerating gene 4 (rhReg4) attenuates the severity of osteoarthritis in OA animal models and may be used as a new method for the treatment of osteoarthritis.

scholarly journals Usefulness of a finger-mounted tissue oximeter with near-infrared spectroscopy for evaluating the intestinal oxygenation and viability in rats

Surgery Today ◽  
2020 ◽  
Author(s):  
Yuhi Suzuki ◽  
Masayoshi Yamamoto ◽  
Kosuke Sugiyama ◽  
Toshiya Akai ◽  
Katsunori Suzuki ◽  
...  
Keyword(s):  
Animal Model ◽  
Intestinal Ischemia ◽  
Near Infrared ◽  
Tissue Oxygenation ◽  
Promising Result ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Histological Score ◽  
Ischemic Tissue ◽  
Normal Intestine

Abstract Purpose To investigate the utility of the device for evaluating intestinal oxygenation and viability using an animal model. Methods Sprague–Dawley rats underwent laparotomy under general anesthesia, and the blood vessels in the terminal ileum were clamped to create ischemia. We measured the regional tissue oxygenation saturation (rSO2) using an oximeter after 1, 3, and 6 h of vessel clamping. Ischemic tissue damage was assessed using a histological score. The intestine was reperfused after each clamping period, and intestinal rSO2 and survival rate were evaluated. Results When reperfusion was performed at 1 and 3 h after ischemia, rSO2 increased after 10 min, and it improved to the same level as for normal intestine after 1 h; all rats survived for 1 week. In contrast, after 6 h of ischemia, rSO2 did not increase after reperfusion, and all animals died within 2 days. The histological scores increased after 1 h of reperfusion, with longer clamping periods. Conclusion A finger-mounted tissue oximeter could evaluate intestinal ischemia and the viability, which is thus considered to be a promising result for future clinical application.

scholarly journals Arum conophalloides Aqueous Extract Induced Hepatotoxicity in Rat; Histopathological, Biochemical, and mir-122 Assessments

MicroRNA ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 224-231
Author(s):  
Amin Derakhshanfar ◽  
Javad Moayedi ◽  
Mahjoob Vahedi ◽  
Abouzar Valizadeh
Keyword(s):  
Aqueous Extract ◽  
Fold Increase ◽  
Normal Structure ◽  
Serum Levels ◽  
Sprague Dawley ◽  
Hydroalcoholic Extract ◽  
Sprague Dawley Rats ◽  
Liver And Kidney ◽  
Biochemical Indices ◽  
Potential Hepatotoxicity

Background: Arum conophalloides (A. conophalloides) is a wild edible delicate plant, widely used in traditional medicine. Objective: This study aimed to examine the effects of A. conophalloides extracts on biochemical, molecular, and histopathological changes in the rat. Methods: Fifty adult male Sprague-Dawley rats were divided into 5 groups (10 each) as follows: G1 or control, received distilled water; G2 and G3, treated with the aqueous extract at doses of 200 and 400 mg/kg; G4 and G5, treated with the hydroalcoholic extract at doses of 200 and 400 mg/kg. Prior to and at the end of the experiments, the serum levels of biochemistry parameters and the relative expression of miR-122 were assessed. Moreover, the liver and kidney tissues were examined microscopically. Results: Liver and kidney tissues showed normal structure in all groups. There were no significant changes in biochemical indices or the expression of miR-122 in the extract-treated groups at the dose of 200 mg/kg. However, the group that received the aqueous extract at the dose of 400 mg/kg exhibited a significantly lower level of HDL, LDL, ALT, and ALP in comparison to the control. Additionally, miR-122 expression in this group exhibited a 10-fold increase (P=0.009). Conclusion: The serum level of hepatocyte-specific miR-122 will be more helpful in detecting hepatic changes in early stages than ALT and AST activity or histopathological evaluations of liver sections. Our findings highlight the potential hepatotoxicity of A. conophalloides aqueous extract in a rat model.

scholarly journals Cardiotoxic effects of pavetamine extracted from Pavetta harborii in the rat

2008 ◽  
Vol 75 (3) ◽  
Author(s):  
L. Hay ◽  
R.A. Schultz ◽  
P.J. Schutte
Keyword(s):  
Heart Failure ◽  
Animal Model ◽  
Carotid Artery ◽  
Plant Material ◽  
Active Component ◽  
Systolic Function ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
The Right ◽  
Induce Heart Failure

Previous studies have shown that crude extracts from Pavetta harborii as well as dried plant material have cardiotoxic effects on rats and sheep that can lead to heart failure. The active component has since been isolated and identified. This substance has been named pavetamine. The aim of this study was to determine whether pavetamine has cardiotoxic effects similar to those seen in previous reports, when administered to rats intraperitoneally. Sprague Dawley rats received two doses, initially 4 mg / kg and then 3 mg / kg pavetamine respectively and were monitored for 35 days before cardiodynamic parameters were measured by inserting a fluid-filled catheter into the left ventricle via the right carotid artery. These values were compared to those of control rats that had received only saline. Pavetamine significantly reduced systolic function and body mass in the treated rats, which indicates that it has the potential to induce heart failure in this animal model.

scholarly journals Paritaprevir and Ritonavir Liver Concentrations in Rats as Assessed by Different Liver Sampling Techniques

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Charles S. Venuto ◽  
Marianthi Markatou ◽  
Yvonne Woolwine-Cunningham ◽  
Rosemary Furlage ◽  
Andrew J. Ocque ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Needle Aspiration ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Time Curve ◽  
Tissue Samples ◽  
Drug Concentrations ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass

ABSTRACT The liver is crucial to pharmacology, yet substantial knowledge gaps exist in the understanding of its basic pharmacologic processes. An improved understanding for humans requires reliable and reproducible liver sampling methods. We compared liver concentrations of paritaprevir and ritonavir in rats by using samples collected by fine-needle aspiration (FNA), core needle biopsy (CNB), and surgical resection. Thirteen Sprague-Dawley rats were evaluated, nine of which received paritaprevir/ritonavir at 30/20 mg/kg of body weight by oral gavage daily for 4 or 5 days. Drug concentrations were measured using liquid chromatography-tandem mass spectrometry on samples collected via FNA (21G needle) with 1, 3, or 5 passes (FNA1, FNA3, and FNA5); via CNB (16G needle); and via surgical resection. Drug concentrations in plasma were also assessed. Analyses included noncompartmental pharmacokinetic analysis and use of Bland-Altman techniques. All liver tissue samples had higher paritaprevir and ritonavir concentrations than those in plasma. Resected samples, considered the benchmark measure, resulted in estimations of the highest values for the pharmacokinetic parameters of exposure (maximum concentration of drug in serum [C max] and area under the concentration-time curve from 0 to 24 h [AUC0–24]) for paritaprevir and ritonavir. Bland-Altman analyses showed that the best agreement occurred between tissue resection and CNB, with 15% bias, followed by FNA3 and FNA5, with 18% bias, and FNA1 and FNA3, with a 22% bias for paritaprevir. Paritaprevir and ritonavir are highly concentrated in rat liver. Further research is needed to validate FNA sampling for humans, with the possible derivation and application of correction factors for drug concentration measurements.

A Novel Rat Model for Comprehensive Microvascular Training of End-to-End, End-to-Side, and Side-to-Side Anastomoses

2019 ◽  
Vol 35 (07) ◽  
pp. 499-504 ◽  
Author(s):  
Xiaoliang Yin ◽  
Gengfan Ye ◽  
Jun Lu ◽  
Lijun Wang ◽  
Peng Qi ◽  
...  
Keyword(s):  
Animal Model ◽  
Average Length ◽  
Proximal Part ◽  
Distal Portion ◽  
Left Renal Artery ◽  
Sprague Dawley ◽  
Anatomical Dissection ◽  
Sprague Dawley Rats ◽  
End To End ◽  
The Right

Background End-to-end, end-to-side, and side-to-side microvascular anastomoses are the main types of vascular bypass grafting used in microsurgery and neurosurgery. Currently, there has been no animal model available for practicing all three anastomoses in one operation. The aim of this study was to develop a novel animal model that utilizes the rat abdominal aorta (AA), common iliac arteries (CIAs), and the median sacral artery (MSA) for practicing these three types of anastomosis. Methods Eight adult Sprague–Dawley rats were anesthetized and then laparotomized. The AA, MSA, and bilateral CIAs were exposed and separated from the surrounding tissues. The length and diameter of each artery were measured. The relatively long segment of the AA without major branches was selected to perform end-to-end anastomosis. One side of the CIAs (or AA) and MSA were used for end-to-side anastomosis. The bilateral CIAs were applied to a side-to-side and another end-to-side anastomosis. Results Anatomical dissection of the AA, CIAs, and MSA was successfully performed on eight Sprague–Dawley rats; four arterial-to-arterial anastomoses were possible for each animal. The AA trunk between the left renal artery and right iliolumbar arteries was 15.60 ± 0.76 mm in length, 1.59 ± 0.15 mm in diameter, for an end-to-end anastomosis. The left CIA was 1.06 ± 0.08 mm in diameter, for an end-to-side anastomosis with the right CIA. The MSA was 0.78 ± 0.07 mm in diameter, for another end-to-side anastomosis with the right CIA or AA. After finishing end-to-side anastomosis in the proximal part of bilateral CIAs, the distal portion was juxtaposed for an average length of 5.6 ± 0.25 mm, for a side-to-side anastomosis. Conclusion This model can comprehensively and effectively simulate anastomosis used in revascularization procedures and can provide more opportunities for surgical education, which may lead to more routine use in microvascular anastomosis training.

scholarly journals Differential Effect of the Dopamine D3 Agonist (±)-7-Hydroxy-2-(N,N-di-n-propylamino) Tetralin (7-OH-DPAT) on Motor Activity between Adult Wistar and Sprague-Dawley Rats after a Neonatal Ventral Hippocampus Lesion

2011 ◽  
Vol 2011 ◽  
pp. 1-8
Author(s):  
Sonia Guzmán-Velázquez ◽  
Linda Garcés-Ramírez ◽  
Gonzalo Flores ◽  
Fidel De La Cruz ◽  
Sergio R. Zamudio
Keyword(s):  
Animal Model ◽  
Motor Activity ◽  
Differential Effect ◽  
Sprague Dawley ◽  
Behavioral Alterations ◽  
Male Adult ◽  
Sd Rats ◽  
Sprague Dawley Rats ◽  
Dopamine D3 ◽  
Genetic And Environmental Factors

The neonatal ventral hippocampal lesion (nVHL) has been widely used as an animal model for schizophrenia. Rats with an nVHL show several delayed behavioral alterations that mimic some symptoms of schizophrenia. Sprague-Dawley (SD) rats with an nVHL have a decrease in D3 receptors in limbic areas, but the expression of D3 receptors in Wistar (W) rats with an nVHL is unknown. The 7-Hydroxy-2-(N,N-di-n-propylamino) tetralin (7-OH-DPAT) has been reported as a D3-preferring agonist. Thus, we investigated the effect of (±)-7-OH-DPAT (0.25 mg/kg) on the motor activity in male adult W and SD rats after an nVHL. The 7-OH-DPAT caused a decrease in locomotion of W rats with an nVHL, but it did not change the locomotion of SD rats with this lesion. Our results suggest that the differential effect of 7-OH-DPAT between W and SD rats with an nVHL could be caused by a different expression of the D3 receptors. These results may have implications for modeling interactions of genetic and environmental factors involved in schizophrenia.

Modulation of in vivo 3-deoxyglucosone levels

2003 ◽  
Vol 31 (6) ◽  
pp. 1433-1437 ◽  
Author(s):  
T.R. Brown ◽  
B. Su ◽  
K.A. Brown ◽  
M.A. Schwartz ◽  
A.M. Tobia ◽  
...  
Keyword(s):  
Fold Increase ◽  
Rat Plasma ◽  
Diabetic Rat ◽  
Kidney Tubules ◽  
Sprague Dawley ◽  
Birth Rates ◽  
Fischer 344 ◽  
Sprague Dawley Rats ◽  
Eker Rat

Fructoselysine 3-phosphate is synthesized in vivo by the recently discovered fructoseamine-3-kinase (F3K) from fructoselysine and ATP and decomposes to lysine, Pi and 3-deoxyglucosone (3DG). This pathway appears to dominate 3DG production in vivo, making it possible to modulate 3DG levels by stimulating or inhibiting the reaction. Present inhibitors are non-reacting substrate analogues with relatively high Ki values and can inhibit F3K sufficiently in vivo to reduce 3DG in diabetic rat plasma by approx. 50%. Stimulation of the F3K pathway by feeding glycated casein causes an increase of 10–20-fold in plasma levels of 3DG and 3-fold in kidney tubules. Consequences of this increase were studied in two systems: the Eker rat, a model of susceptible kidney tubules; and birth rates in two rat strains. In both cases substantial pathological effects were observed. In the Eker rats, an approx. 3-fold increase in kidney lesions was observed (P<0.00001). In both Fischer 344 and Sprague–Dawley rats, birth rates were reduced by 56% (P<0.0001) and 12% (P<0.015) respectively. These results suggest that inhibition of F3K is a promising new therapeutic target for diabetic complications, as well as other 3DG-dependent pathologies.

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